Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH 45229-3039, USA.
J Immunol. 2010 Jan 15;184(2):975-83. doi: 10.4049/jimmunol.0900650. Epub 2009 Dec 9.
Surfactant protein B (SP-B) proprotein contains three saposin-like protein (SAPLIP) domains: a SAPLIP domain corresponding to the mature SP-B peptide is essential for lung function and postnatal survival; the function of SAPLIP domains in the N-terminal (SP-BN) and C-terminal regions of the proprotein is not known. In the current study, SP-BN was detected in the supernatant of mouse bronchoalveolar lavage fluid (BALF) and in nonciliated bronchiolar cells, alveolar type II epithelial cells, and alveolar macrophages. rSP-BN indirectly promoted the uptake of bacteria by macrophage cell lines and directly killed bacteria at acidic pH, consistent with a lysosomal, antimicrobial function. Native SP-BN isolated from BALF also killed bacteria but only at acidic pH; the bactericidal activity of BALF at acidic pH was completely blocked by SP-BN Ab. Transgenic mice overexpressing SP-BN and mature SP-B peptide had significantly decreased bacterial burden and increased survival following intranasal inoculation with bacteria. These findings support the hypothesis that SP-BN contributes to innate host defense of the lung by supplementing the nonoxidant antimicrobial defenses of alveolar macrophages.
表面活性蛋白 B (SP-B) 前蛋白含有三个类 Saposin 蛋白 (SAPLIP) 结构域：一个 SAPLIP 结构域与成熟 SP-B 肽相对应，对肺功能和出生后存活至关重要；前蛋白 N 端 (SP-BN) 和 C 端区域中 SAPLIP 结构域的功能尚不清楚。在本研究中，SP-BN 被检测到在小鼠支气管肺泡灌洗液 (BALF) 的上清液中，以及非纤毛细支气管细胞、肺泡 II 型上皮细胞和肺泡巨噬细胞中。rSP-BN 间接促进了巨噬细胞系对细菌的摄取，并在酸性 pH 值下直接杀死细菌，与溶酶体、抗菌功能一致。从 BALF 中分离出的天然 SP-BN 也能杀死细菌，但仅在酸性 pH 值下；SP-BN Ab 完全阻断了 BALF 在酸性 pH 值下的杀菌活性。过表达 SP-BN 和成熟 SP-B 肽的转基因小鼠在鼻腔接种细菌后，细菌负荷显著降低，存活率增加。这些发现支持了这样一种假设，即 SP-BN 通过补充肺泡巨噬细胞的非氧化抗菌防御来促进肺的先天宿主防御。
